Phase I trial of oral talactoferrin alfa in refractory solid tumors

  • Teresa G. HayesEmail author
  • Gerald F. Falchook
  • Gauri R. Varadhachary
  • Dori P. Smith
  • Lisa D. Davis
  • Hari M. Dhingra
  • Benjamin P. Hayes
  • Atul Varadhachary
Phase I Studies


Background: Lactoferrin is an iron-binding glycoprotein first identified in breast milk as a protein product of mammary epithelial cells. Its immunomodulatory functions include activation of NK and lymphokine-activated killer cells and enhancement of PMN and macrophage cytotoxicity. Studies in animal models have shown promising anti-cancer activity. The purpose of the present study was to evaluate the safety and tolerability of talactoferrin alfa (talactoferrin; TLF) in humans, as well as pharmacokinetics and pharmacodynamics. Methods: Ten adult patients with progressive advanced solid tumors who had failed conventional chemotherapy were administered oral TLF at doses from 1.5 to 9 g/day, using a 2 weeks on, 2 weeks off schedule. Patients were evaluated for drug toxicity, tumor growth rate, talactoferrin pharmacokinetics and cytokine markers. Results: Talactoferrin was very well tolerated. No hematological, hepatic, or renal toxicities were reported. A single patient had Grade 2 diarrhea, and there were no Grade 3 or 4 toxicities. Following oral administration, significant levels of talactoferrin were undetectable in circulation, but a statistically significant increase in circulating IL-18, a pharmacodynamic indicator of talactoferrin activity, was observed. Of the eight patients who were radiologically evaluable, five (63%) had stable disease by RECIST criteria two months after start of therapy, including one patient with a minor response. Seven patients (88%) had a decrease in their tumor growth rate. The three patients with non-small cell lung cancer (NSCLC) all survived for at least one year following the start of talactoferrin monotherapy. Conclusions: Talactoferrin is a promising, well-tolerated new agent that should be evaluated further in patients with refractory metastatic cancer.

Key Words

talactoferrin nonsmall cell lung cancer refractory cancer 


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Copyright information

© Springer Science + Business Media, LLC 2005

Authors and Affiliations

  • Teresa G. Hayes
    • 1
    • 2
    Email author
  • Gerald F. Falchook
    • 1
  • Gauri R. Varadhachary
    • 1
  • Dori P. Smith
    • 1
  • Lisa D. Davis
    • 1
  • Hari M. Dhingra
    • 1
  • Benjamin P. Hayes
    • 1
  • Atul Varadhachary
    • 1
  1. 1.Michael E. DeBakey VA Medical Center and Baylor College of MedicineHoustonUSA
  2. 2.VA 111H, Michael E. DeBakey VA Medical CenterHoustonUSA

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